Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with poor survival rates in part due to the fact that most cases are initially diagnosed too late in the course of the disease for potentially curative resection. With the highest mortality rate of any cancer, PDAC has a 5-year survival rate less than 5%. Despite extensive efforts in recent years, advancement in treatments has been meager. Surgical resection remains the only curative intervention, but only 18% of patients are diagnosed at early stages when surgical resection is an option. The remaining 82% of patients present with advanced disease at diagnosis. For these patients, disease management is limited to palliation. A substantial determinant for the lethality of PDAC is the late presentation due to asymptomatic development and earlier detection would improve outcomes by identifying the disease while still amenable to potentially curative intervention.
Screening programs designed to detect early stage PDAC in asymptomatic populations face considerable challenges, not the least of which is the need for a highly accurate test that would limit false-positive identifications in this relatively rare disease. On the basis of the differential accumulation of mutations in primary and metastatic lesions, a recent study estimated an average of 11.7 years elapsed from tumor initiation to overt cancer development and an average of 6.8 years elapsed between the development of overt cancer and the development of metastatic disease. The finding that pancreatic tumors are present for a significant period of time before clinical manifestation emphasizes the potential for screening and early detection. Unfortunately, even the best currently available blood-based biomarker, CA 19-9, has significant shortcomings, including unacceptably low accuracy, that limit its use to monitoring disease progression. No single biomarker or combinations of a few biomarkers has emerged that markedly improves on CA 19-9 diagnostic accuracy.
There is a great need to identify biomarkers that can be combined into an accurate and cost-effective biomarker panel that would be an useful screening tool in asymptomatic populations. The present invention addresses this need by providing compositions and methods for the diagnosis of early stage PDAC. Related methods and advantages are provided as well.